Diethyl Ether → 1,1-Dimethylethyl (4R,6R)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetate

HRID 5707Notes

Reaction equation

[C:1]([CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([OH:15])=[O:14])[CH2:5]1)#[N:2].[C:16](O)([CH3:19])([CH3:18])[CH3:17].C1(N=C=NC2CCCCC2)CCCCC1.C(OCC)C>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]1)#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

(±)-cis-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid (3.72 g, 17.44 mmol) is dissolved in 20 mL of dichloromethane, cooled to 0° C. and 0.2 g of 4-dimethylaminopyridine (DMAP) is added, followed by t-butyl alcohol and followed by 4.32 g of dicyclohexylcarbodiimide (DCC). This solution is allowed to slowly warm to room temperature over a 76.5-hour period. Thin layer chromotography (TLC) shows mainly product, and some slightly lower Rf by-products. The mixture is stirred one hour and 50 mL of dichloromethane is added and stirring continues five hours. An additional 100 mL of diethyl ether is added and the mixture filtered. The precipitate is washed with diethyl ether. The filtrate is concentrated to an oil. The crude product is chromatographed on silica gel eluting with 4:1 hexane:ethyl acetate. The eluate is concentrated to yield (±)-cis-1,1-dimethylethyl 6-(cyanomethyl)-2,2-dimethyl-1,3-dioxane-4-acetate.

Workup

temperatureto slowly warm to room temperature over a 76.5-hour period
stirringstirring
waitcontinues five hours
filtrationthe mixture filtered
washThe precipitate is washed with diethyl ether
concentrationThe filtrate is concentrated to an oil
customThe crude product is chromatographed on silica gel eluting with 4:1 hexane
concentrationThe eluate is concentrated

Sources & evidence

ORD record: ord-eebe7f54970b4c3a9ecf4c7b08834f14
Source dataset: uspto-grants-1993_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05245047

Reaction notes

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